QuadBase2: web server for multiplexed guanine quadruplex mining and visualization

DNA guanine quadruplexes or G4s are non-canonical DNA secondary structures which affect genomic processes like replication, transcription and recombination. G4s are computationally identified by specific nucleotide motifs which are also called putative G4 (PG4) motifs. Despite the general relevance of these structures, there is currently no tool available that can allow batch queries and genome-wide analysis of these motifs in a user-friendly interface. QuadBase2 (quadbase.igib.res.in) presents a completely reinvented web server version of previously published QuadBase database. QuadBase2 enables users to mine PG4 motifs in up to 178 eukaryotes through the EuQuad module. This module interfaces with Ensembl Compara database, to allow users mine PG4 motifs in the orthologues of genes of interest across eukaryotes. PG4 motifs can be mined across genes and their promoter sequences in 1719 prokaryotes through ProQuad module. This module includes a feature that allows genome-wide mining of PG4 motifs and their visualization as circular histograms. TetraplexFinder, the module for mining PG4 motifs in user-provided sequences is now capable of handling up to 20 MB of data. QuadBase2 is a comprehensive PG4 motif mining tool that further expands the configurations and algorithms for mining PG4 motifs in a user-friendly way.

[1]  A. Phan,et al.  Bulges in G-quadruplexes: broadening the definition of G-quadruplex-forming sequences. , 2013, Journal of the American Chemical Society.

[2]  Oleg Kikin,et al.  QGRS Mapper: a web-based server for predicting G-quadruplexes in nucleotide sequences , 2006, Nucleic Acids Res..

[3]  Oleg Kikin,et al.  GRSDB2 and GRS_UTRdb: databases of quadruplex forming G-rich sequences in pre-mRNAs and mRNAs , 2007, Nucleic Acids Res..

[4]  N. Maizels,et al.  G-quadruplexes are genomewide targets of transcriptional helicases XPB and XPD , 2014, Nature chemical biology.

[5]  Jesse M. Platt,et al.  Detection of G-quadruplex DNA in mammalian cells , 2013, Nucleic acids research.

[6]  G. Hong,et al.  Nucleic Acids Research , 2015, Nucleic Acids Research.

[7]  A. Phan,et al.  Human telomeric DNA: G-quadruplex, i-motif and Watson-Crick double helix. , 2002, Nucleic acids research.

[8]  S. Mirkin.  Discovery of alternative DNA structures: a heroic decade (1979-1989). , 2008, Frontiers in bioscience : a journal and virtual library.

[9]  J. Postberg,et al.  Probing telomeric G-quadruplex DNA structures in cells with in vitro generated single-chain antibody fragments. , 2010, Methods in molecular biology.

[10]  Stephen Neidle,et al.  Loop-length-dependent folding of G-quadruplexes. , 2004, Journal of the American Chemical Society.

[11]  Jean-Louis Mergny,et al.  Re-evaluation of G-quadruplex propensity with G4Hunter , 2016, Nucleic acids research.

[12]  G. Garg,et al.  Guanine quadruplex DNA structure restricts methylation of CpG dinucleotides genome-wide. , 2010, Molecular bioSystems.

[13]  Shengyong Yan,et al.  Existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy , 2013, Scientific Reports.

[14]  Jean-Michel Marin,et al.  Unraveling cell type–specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs , 2012, Nature Structural &Molecular Biology.

[15]  T. Bryan,et al.  Physiological relevance of telomeric G‐quadruplex formation: a potential drug target , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[16]  A. Serero,et al.  Short loop length and high thermal stability determine genomic instability induced by G‐quadruplex‐forming minisatellites , 2015, The EMBO journal.

[17]  Ram Krishna Thakur,et al.  Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression , 2008, Nucleic acids research.

[18]  K. Woodford,et al.  CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro. , 1995, Nucleic acids research.

[19]  Dinshaw J. Patel,et al.  Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics , 2007, Nucleic acids research.

[20]  D. Patel,et al.  Identifying hydrogen bond alignments in multistranded DNA architectures by NMR. , 2002, Accounts of chemical research.

[21]  Stephen Neidle,et al.  Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? , 2011, Nature Reviews Drug Discovery.

[22]  V. K. Yadav,et al.  Genome-Wide Analyses of Recombination Prone Regions Predict Role of DNA Structural Motif in Recombination , 2009, PloS one.

[23]  S. Neidle,et al.  Highly prevalent putative quadruplex sequence motifs in human DNA , 2005, Nucleic acids research.

[24]  Laty A. Cahoon,et al.  An Alternative DNA Structure Is Necessary for Pilin Antigenic Variation in Neisseria gonorrhoeae , 2009, Science.

[25]  Shantanu Chowdhury,et al.  QuadBase: genome-wide database of G4 DNA—occurrence and conservation in human, chimpanzee, mouse and rat promoters and 146 microbes , 2007, Nucleic Acids Res..

[26]  Shankar Balasubramanian,et al.  Prevalence of quadruplexes in the human genome , 2005, Nucleic acids research.

[27]  Paramjeet Singh Bagga,et al.  QGRS-H Predictor: a web server for predicting homologous quadruplex forming G-rich sequence motifs in nucleotide sequences , 2012, Nucleic Acids Res..

[28]  H. Gautam,et al.  Genome-wide study predicts promoter-G4 DNA motifs regulate selective functions in bacteria: radioresistance of D. radiodurans involves G4 DNA-mediated regulation , 2012, Nucleic acids research.

[29]  Alessandro Vullo,et al.  Ensembl 2015 , 2014, Nucleic Acids Res..

[30]  Rashi Halder,et al.  Genome-wide analysis predicts DNA structural motifs as nucleosome exclusion signals. , 2009, Molecular bioSystems.

[31]  Lawrence D'Antonio,et al.  Computational methods for predicting intramolecular G-quadruplexes in nucleotide sequences , 2004, Proceedings. 2004 IEEE Computational Systems Bioinformatics Conference, 2004. CSB 2004..

[32]  Han Min Wong,et al.  Stable G-quadruplexes are found outside nucleosome-bound regions. , 2009, Molecular bioSystems.

[33]  Alessandro Vullo,et al.  The Ensembl REST API: Ensembl Data for Any Language , 2014, Bioinform..

[34]  S. Balasubramanian,et al.  Quantitative visualization of DNA G-quadruplex structures in human cells. , 2013, Nature chemistry.

[35]  Mitali Mukerji,et al.  Genome-wide prediction of G4 DNA as regulatory motifs: role in Escherichia coli global regulation. , 2006, Genome research.

[36]  John D. Hunter,et al.  Matplotlib: A 2D Graphics Environment , 2007, Computing in Science & Engineering.

[37]  D. Davies,et al.  Helix formation by guanylic acid. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[38]  N. Maizels,et al.  Gene function correlates with potential for G4 DNA formation in the human genome , 2006, Nucleic acids research.

[39]  Katrin Paeschke,et al.  DNA Replication through G-Quadruplex Motifs Is Promoted by the Saccharomyces cerevisiae Pif1 DNA Helicase , 2011, Cell.

[40]  D. Bearss,et al.  Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[41]  J. Sale,et al.  PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells , 2016, Molecular cell.

[42]  K. Fox,et al.  Inosine substitutions demonstrate that intramolecular DNA quadruplexes adopt different conformations in the presence of sodium and potassium. , 2005, Bioorganic & medicinal chemistry letters.

[43]  H. Nakagama,et al.  Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription , 2009, Nucleic acids research.

[44]  Manikandan Paramasivam,et al.  The KRAS Promoter Responds to Myc-associated Zinc Finger and Poly(ADP-ribose) Polymerase 1 Proteins, Which Recognize a Critical Quadruplex-forming GA-element* , 2010, The Journal of Biological Chemistry.

[45]  Katrin Paeschke,et al.  DNA secondary structures: stability and function of G-quadruplex structures , 2012, Nature Reviews Genetics.